UCLA Researchers Discover Genes Linked To Lymphoma, Opening Way For New Targeted Drugs

Lymphoma is a blood cancer that affects more than 60,000 Americans each year. Researchers at The University of California Los Angeles have identified genes that when inactivated help cause B-cell non-Hodgkin’s lymphoma (NHL).

These genetic defects may also be involved in promoting the formation of other cancers since they can inactivate normal tumor-suppressing gene activities in a range of cell types.The team led by Michael Teitell, M.D., Ph.D., and funded by The Leukemia & Lymphoma Society, used genetically engineered mice to accurately mimic human B-cell cancers. They had previously published research in which they identified frequent genetic abnormalities in cancer cells from NHL patients — namely defects in the TCL1 gene — and showed that TCL1 abnormalities can cause NHL in mice when accompanied by additional genetic defects. Now, they have found some of these cancer collaborators.Teitell’s team used a powerful genetic technique called “restriction landmark genomic scanning” (RLGS) to find genes that work with abnormal TCL1 to promote lymphoma formation. These genes are inactivated in lymphomas by defects known as DNA hypermethylation. The breakthrough research, published in the journal Oncogene, is likely to help in the development of new targeted drugs for NHL patients.The researchers are working to determine which hypermethylation gene defects also occur in human lymphomas, at which point they will be ready to help develop new targeted therapies for NHL patients. Drugs that target DNA hypermethylation are already known to have anti-cancer activity. The drug Decitabine (Dacogen(R); SuperGen/MGI Pharma) has recently been approved by the U.S. Food and Drug Administration to treat patients with myelodysplastic syndrome, and is being tested in other cancers. Teitell’s findings suggest that such drugs should be tested for anti-lymphoma activity.Dr. Teitell is the recipient of a Society Scholar Award — a program that provides funding to highly qualified investigators conducting original research on leukemia, lymphoma or myeloma.”The goal of the Scholar program is to help advance promising original research with the potential to have the highest impact on blood cancers,” said Deborah Banker, Ph.D., the Society’s vice president for research communications. “Dr. Teitell’s research shows great promise in leading to more effective treatments for NHL patients.”Dr. Teitell said that the Society’s support was fundamental in moving his research forward. “I am truly grateful to The Leukemia & Lymphoma Society for having confidence in our work and providing our group with this funding,” he said. “I am optimistic that our efforts will improve outcomes for NHL patients.”(Source: Oncogene : The University of California Los Angeles : February 2007.)